title: Elevated atherogenic index following oral administration of quaternized polyamine nanogels.
abstract: Quaternized polyamine nanogels possessing poly(ethylene glycol) (PEG)-tethered chains as the surface layer were prepared by redox-initiated emulsion polymerization of 2-(N,N-diethylamino)ethyl methacrylate (EAMA) in the presence of vinylbenzyl-ended poly(ethylene glycol) (PEG-CH2PhCHCH2), followed by quaternization with methyl iodide (QNG-I). QNG-I absorbed taurocholic acid regardless of environmental pH, because of the fixed positive charge of QNG-I. Oral administration of polyamine nanogels into mice tended to cause intestinal retention, with accumulation of up to 70% of the initial dose. Levels of low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice effectively decreased following oral administration of QNG-I. Interestingly, oral administration of QNG-I increased the levels of high-density lipoprotein cholesterol (HDL-C), resulting in an extremely high atherogenic index. Iodide counter-anions in QNG-I played an important role in the increase in HDL-C levels.
authors.affiliation: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
authors.affiliation: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Department of Materials Science, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
authors.affiliation: Department of Molecular Innovation in Lipiodology, National Cerebral and Cardiovascular Center Research Institute, Fujishiro-dai 5-7-1, Suita, Osaka 565-8565, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
mesh_terms: D000818:Animals; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000080385:Nanogels; D011073:Polyamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000080385:Nanogels; D011073:Polyamines; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: Atherogenic index; Bile acid adsorbent; Oral nanotherapeutics; Quaternized nanogels